High LDL-Cho-specific circulating miRNAs are predicted to be involved in metabolomic alterations and the development of a wide range of related diseases - target gene prediction and GO analysis

Background and objectives: The 2019 National Health and Nutrition Survey reported that more than 30% of men in their 40s have a high LDL cholesterol (LDL-Cho) level (F formula). Micro (mi) RNAs are small RNAs that collectively suppress the expression of various genes. Among the miRNAs are blood-secreted miRNAs (circulating miRNAs) that are secreted from secreting cells and act on target cells through the blood. In this study, we performed comprehensive identification of high LDL-Cho-specific circulating miRNAs, target gene prediction and Gene Ontology (GO) analysis, and aimed to predict the effect on metabolism and causality with related diseases. Methods: Serum miRNA expression in healthy subjects and subjects with high LDL-Cho (serum LDL-Cho > 140 mg/dL) who had IC in men in their 40s and 50s was comprehensively analyzed by microarray, target gene prediction was performed using Targetscan and miRDB, and GO analysis was performed in conjunction with the Human Metabolome Database and Disease Jensen Database by Shiny GO application. Results: We identified 30 circulating miRNAs with variable expression levels specific to high LDL-Cho, of which 4 miRNAs with increased expression were predicted to be involved in the alterations of metabolites such as phosphatidic acid (PA) (16:0 / 16:0) (Enrichment FDR = 0.0128; the same hereinafter), phosphatidylinositol (PI) (16:0 / 18:0) (0.0128), LysoPA (18:2 (9Z, 12Z) / 0:0) (0.0207), cytidine monophosphate (0.0261), and pyruvic acid (0.0354). Surprisingly, these four miRNAs were also predicted to be involved in the development of diseases associated with high LDL-Cho, including carcinoma (Enrichment FDR = 1.51E-177; the same hereinafter), acquired metabolic disease (8.51E-06), cardiovascular system disease (0.000864) and Alzheimer's disease (0.0103). Conclusions: The results of this study suggested that the identified high LDL-Cho-specific circulating miRNAs are associated with metabolic alterations and the development of related diseases. In the future, we would like to describe the blood expression levels of the above miRNAs for each risk group with different numbers of important risk factors such as aging (men > 45 years), hypertension, diabetes mellitus, smoking, family history of coronary artery disease and low HDL cholesterol (< 40 mg/dL) for high LDL-Cho, and apply them to diagnostic markers.